Robert L. Adams

Photothermal effects on murine mammary tumors using indocyanine green and an 808-nm diode laser: an in vivo efficacy study.

Murine mammary tumors were treated using indocyanine green and an 808 nm diode laser, and the in vivo chromophore-enhanced photothermal effects on the tumor burden and on tumor rat survival were investigated. The power of the laser was selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent aqueous indocyanine green solution in a volume of 100-200 microliters was administered in situ, either acutely or 24 h prior to the treatment. The photothermal interaction was apparent under all our treatment conditions with a well-defined spatial containment in this study and the tumor growth was slowed after treatment. The post-treatment observation showed tumor recurrence and metastasis; no long-term survival was achieved with the single application of laser in conjunction with indocyanine green. Our results pose a question on the efficacy of the photothermal interaction even though tumor cell destruction can be achieved in a large and controlled scale. However, this highly selective photothermal impact on the tumor tissue did suggest that this method be applied repeatedly to be more effective and be used as the precursor of other modalities, such as chemotherapy, radiation therapy, immunotherapy, and surgery.

Laser-photosensitizer assisted immunotherapy: A novel modality for cancer treatment

Photosensitizer-enhanced laser treatment, where dyes are activated in situ by lasers of appropriate wavelengths, provides highly selective tissue destruction, both spatially and temporally, through photophysical reactions. Although laser-sensitizer treatment for cancer can achieve a controlled local tumor cell destruction on a large scale, total tumor eradication may not be accomplished because of the incomplete local tumor killing or the presence of tumor metastases, or both. The long-term control of cancer depends on the host immune surveillance and defense systems in which both cell-mediated and humoral responses are critical. In this study we report a novel minimally invasive cancer treatment combining the laser photophysical effects with the photobiological effects. Irradiation of a rat mammary tumor by an 805 nm diode laser, after an intratumor administration of a specific photosensitizer, indocyanine green in a glycated chitosan gel, caused immediate photothermal destruction of neoplastic cells. Concomitantly this treatment stimulated the immunological defense system against residual and metastatic tumor cells. Increases in survival rate and in the eradication of tumor burden, both primary and metastatic, were observed after this treatment. Furthermore, the resistance of successfully treated rats to tumor rechallenge demonstrated a long-lasting systemic effect of the treatment. These findings indicate that our treatment has triggered a specific humoral immune response in the tumor-bearing rats.

Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser

Rat mammary tumors were treated using an 808-nm diode laser in a power range of 3-15 W. Photothermolysis was selectively enhanced by the chromophore indocyanine green (ICG), which has an absorption peak corresponding to the laser wavelength. ICG, injected into neoplastic tissues 24 h before laser exposure, was retained in sufficient quantity to produce a strong photothermal reaction. With appropriate laser power and adequate irradiation duration, laser energy could inflict severe photothermal damage to the entire targeted tumor tissue while leaving the skin and other interdicted tissue undamaged. Higher laser powers (10-15 W) produced more surface damage that limited light transmission and as a result gave rise to reduced regions of thermal destruction. Post-treatment observation revealed the survival of numerous tumor cells. This finding questions the long term efficacy of the photothermal effect of a single treatment using the combination of the ICG and the diode laser, particularly in the absence of other modalities.

Chromophore-enhanced laser-tumor tissue photothermal interaction using an 808-nm diode laser

A diode laser was used to irradiate tumor tissue, with indocyanine green as the chromophore. The 808-nm wavelength radiation falls within the absorption peak of the chromophore (about 780 nm). The preliminary results in this report revealed clear and significant coupling of this laser and indocyanine green in laser-tissue photothermal interaction. The chromophore targeted tissue showed laser damage while peripheral tissues remained intact. Without the chromophore, this laser inflicted no apparent tissue damage in the non-contact mode with irradiance up to 1755 J/cm2.

Indocyanine green in-situ administration and photothermal destruction of tumor cells using an 808-nm diode laser

Laser tumor tissue photothermal interaction was studied using an 808 nm diode laser and indocyanine green as the photosensitizer. This in vitro study employed laser power in the range of 3 to 5 watts and an aqueous ICG solution that was administered to murine mammary tumor tissue by intralesional injection. Histology revealed a highly selective photothermal tumor tissue destruction at the center of the ICG injection, while the tumor cells not in the ICG area were spared. Also studied was the retention of photosensitizer in tissue following different methods of administration. The absorption spectra of tissue in the range of 400 to 900 nm were obtained at different time intervals after ICG injections for liver and kidney tissue, as well as tumor tissue. Our results showed, shortly after intracardiac injection, a rapid increase of ICG concentration in liver and virtually no accumulation of ICG in the subcutaneous tumor tissue. In contrast, the intratumoral-injected ICG remained in the tumor with sufficient concentration for a duration up to 48 hours, particularly in the case of well- circumscribed tumors. The combination of the in situ ICG administration and the 808-nm diode laser provided selective and controllable cancer tissue destruction when appropriate laser powers and dosage of ICG were employed.

Antitumor immune responses induced by photodynamic immunotherapy in rats

A new laser immunotherapy was used to treat metastatic mammary rat tumors. This new modality consists of three components: a near-infrared diode laser, a photosensitizer, and an immunoadjuvant. The sensitizer-adjuvant solution was injected directly to the tumor, followed by a non-invasive laser application. The new method resulted in total eradication of the treated primary tumors and eradication of untreated metastases at remote sites. Observed was the long-term survival of treated tumor-bearing rats: up to 120 days after tumor inoculation, a 300% increase in survival length compared with untreated control tumor-bearing rats. In addition, the successfully treated rats were refractory to tumor rechallenge with 10 times of the original tumor dose. Fluorescein and peroxidase immunochemical assays were also performed using sera from cured rats as the primary antibody. Strong antibody binding to both live and preserved tumor cells was observed. Western blot analysis, using the cured rat serum as primary antibody also showed distinctive protein binding, suggesting the induction of tumor-specific humoral immune response. These results indicated that an immune response was induced by the treatment of laser, photosensitizer and immunoadjuvant.

The Effect of Phenylephrine on Müller Muscle

PURPOSE The blepharogram technique is used to study the effect of a drug on blinking. The authors show that ocular instillation of phenylephrine, a stimulant of Müller muscle of the eyelid, accelerates the up phase of the blink. METHODS Motion of a tiny search coil glued to the eyelid moving in a weak magnetic field modifies an induced alternating current which is amplified and used to display the position of the upper eyelid in degrees on the ordinate of a graph with time in milliseconds on the abscissa. The graph is called a blepharogram. Blepharogram studies and individual blink analysis show the effect of phenylephrine on eyelid motion (blinking). RESULTS Instillation of phenylephrine accelerated the up phase of the blink in all ten experimental subjects. In 65% of subjects, phenylephrine also produced or increased newly described N and M blepharogram patterns. CONCLUSION This is the first instrumental detection of the effect of a pharmacologic agent on eyelid motion. The blepharogram technique provides insight into eyelid physiology and can be used to study any neuromuscular condition that affects eyelid motion.

Ultrasonic Characterization of Composite Microstructure

In this work, nondestructive methods for the quantitative evaluation of composite microstructure are described. Parameters of interest in this regard might include fiber volume fraction, porosity, degree of cure (thermoset resins) and crystallinity (thermoplastic resins). These methods rely upon the high degree of accuracy which can be obtained with ultrasonic measurements of acoustic velocities; hence the mechanical properties of the material, and well established composite micromechanics relationships between elastic properties and composite microstructure. This results in sets of nonlinear equations which can be solved for the unknown microstructural parameters.

Laser-tissue photobiological interaction: a new mechanism for laser sensitizer immunoadjuvant treatment of metastatic cancers

Photophysical reactions have been the focus of laser-tissue interactions. However, these interactions usually have localized and short-term effect, hence only resulting in limited success against systemic lesions, especially against metastatic tumors. Could laser induce a photobiological reaction, specifically a long-term reaction in cancer treatment. Our experimental results on treatment of rat breast cancer indicated that a systemic and long term response against the tumors could be stimulated by a new laser-sensitizer-immunoadjuvant treatment. Long term impact of our method was observed; survival tumor rats and apparent ability against tumor re-challenge. The long term effect was also confirmed by our histochemical studies. Our results pointed to a humoral immune response. A new mechanism of laser-tissue interaction, namely laser-sensitizer- immunoadjuvant induced photobiological reaction, may prove to be crucial in laser cancer treatment.

Effects of indocyanine green in treatment of murine mammary tumor by an 808-nm diode laser: an in-vivo study

Indocyanine green was used to enhance laser-induced photothermal destruction of murine mammary tumor cells. The 808-nm diode laser used in these experiments matches the absorption peak of the indocyanine green. The combination of the laser and in situ administration of aqueous ICG provided a highly selective photothermal destruction pattern of the tumor tissue. Histology showed that within the power range of 3 to 5 watts. The ICG- targeted tumor tissues were fatally injured, while the peripheral tissues such as skin and other interdicting tissue not containing ICG were spared. Higher powers (10 to 15 watts) could inflict severe surface damage but only resulted in limited tissue penetration. Post-treatment observation also revealed surviving tumor cells, the cause of which might be the non-uniform distribution of ICG as well as the random scattering of photons inside tissue. After laser-ICG treatment, the tumor continued to grow, but at a slower rate, and to metastasize, leading to the death of the rats. The findings of our experiments question the long-term efficacy of the photothermal effect of a single treatment using the ICG and diode laser. However, the controlled killing of tumor cells on a large scale may be proven crucial when the treatment is applied repeatedly and/or in an earlier stage so that tumor growth could be stopped and metastases prevented. This photothermal interaction may also be effective when used in conjunction with other modalities.